Two important effects which result from exposure of the mammalian liver to chemical carcinogens are alterations in phenotypic expression (especially altered are control mechanisms) and in chromosome composition. We propose to continue and extend our study of the pattern of alteration of selected specialized functions of hepatocytes and their chromosome structure following exposure to carcinogens; and the hepatomas which result. To accomplish the former, we will apply the technique of immunoelectrophoresis radioautography whereby we can examine the production of 15 plasma proteins (or more) by aliquots of tissue as small as 75mg. In addition, using highly specific antisera, we will examine tissue synthesis and circulating levels of alpha fetoprotein. Both functions will be related to isoenzyme alterations, synthesis of alpha 1-anti trypsin and morphologic alterations to determine if specific patterns are related to carcinogenic evolution. These tissues will also be analyzed for chromosome composition and structure by our modifications of the quinacrine fluorescent and giemsa banding techniques. All forms of analysis will also be applied to lines of transplantable hepatomas which have been developed in this laboratory and which were derived from highly characterized primary tumors. We will also attempt to "select" specific phenotype: chromosomal patterns in such tumors.